Ingestion of Lactobacillus intestinalis and Lactobacillus reuteri causes depression- and anhedonia-like phenotypes in antibiotic-treated mice via the vagus nerve

<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>The brain–gut–microbiota axis plays a role in the pathogenesis of stress-related disorders such as depression. In this study, we examined the effects of fecal microbiota transplantation (FMT) in mice with antibiotic-treated microbiota depletion.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>The fecal microbiota was obtained from mice subjected to chronic social defeat stress (CSDS) and control (no CSDS) mice. FMT from these two groups was performed to antibiotic-treated mice. 16S rRNA analysis was performed to examine the composition of gut microbiota. Furthermore, the effects of subdiaphragmatic vagotomy in depression-like phenotypes after ingestion of microbes were examined.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>The ingestion of fecal microbiota from CSDS-susceptible mice resulted in an anhedonia-like phenotype, higher plasma levels of interleukin-6 (IL-6), and decreased expression of synaptic proteins in the prefrontal cortex (PFC) in antibiotic-treated mice but not in water-treated mice. 16S rRNA analysis suggested that two microbes (<jats:italic>Lactobacillus intestinalis</jats:italic>and<jats:italic>Lactobacillus reuteri</jats:italic>) may be responsible for the anhedonia-like phenotype in antibiotic-treated mice after FMT. Ingestion of these two microbes for 14 days led to depression- and anhedonia-like phenotypes, higher plasma IL-6 levels, and decreased expression of synaptic proteins in the PFC of antibiotic-treated mice. Interestingly, subdiaphragmatic vagotomy significantly blocked the development of behavioral abnormalities, elevation of plasma IL-6 levels, and downregulation of synaptic proteins in the PFC after ingestion of these two microbes.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>These findings suggest that microbiota depletion using an antibiotic cocktail is essential for the development of FMT-induced behavioral changes and that the vagus nerve plays a key role in behavioral abnormalities in antibiotic-treated mice after the ingestion of<jats:italic>L. intestinalis</jats:italic>and<jats:italic>L. reuteri</jats:italic>. Therefore, it is likely that the brain–gut–microbiota axis participates in the pathogenesis of depression via the vagus nerve.</jats:p></jats:sec>